Page 435 - Environmental Nanotechnology Applications and Impacts of Nanomaterials

Toxicological Impacts of Nanomaterials 415

of nanoparticles adsorption on the cell membrane and, second, to the for-
mation of nanoparticles clusters. Albumin coating on AMNP hampers
their interactions with the membrane, probably due to a steric effect that
reduces the accessibility of nanoparticles for the positively charged bind-
ing sites on the cell membrane and on the other part diminishes the
aggregation of the nanoparticles. Thus, the nonspecific adsorption of
nanoparticles on the cell membrane is considerably reduced by albumin
coating and, as a consequence, cell internalization is limited to the fluid
phase endocytotic pathway.
Further research is needed to determine if the electrostatic forces
bound between cationic sites on the cell membrane and anionic nanopar-
ticles are due to their internalization or through a physical mechanism.
How are cationic sites on the cell, present at a low density, able to attract
anionic nanoparticles? A full explanation for the surprisingly high level
of cell uptake that is achieved using anionic nanoparticles is lacking.
The magnetic resonance contrast properties of this DMSA-coated
nanomaghemite, free of any dextran coating with a negative surface
charge, has been studied (Billotey et al., 2003). The uptake of nanopar-
ticles in macrophages was quantified using electron spin resonance.
The precise determination of particle load in cells allows for quantita-
tive comparison in contrast to the cell’s internalized particles vs. dis-
persed isolated particles, and to demonstrate a drastic decrease of
longitudinal relaxivity due to cell internalization. The effect on longi-
tudinal relaxivity is explained by a saturation of the relaxing effect of
the particles confined within the micrometric endosomes.
Berry and coworkers (2003) have investigated the in vitro influence
of dextran- or albumin-coated iron oxide nanoparticles in fibroblasts, as
compared to those underivatized, using bromodeoxyuridine (BrdU)
uptake, light microscopy, scanning electron microscopy, fluorescence of
the cytoskeletal filaments (F-actin and vinculin), and clathrin localiza-
tion. Their results strengthened the role of the shell core of iron oxide
nanoparticles in cell responses. Indeed, dextran-derivatized, albumin-
derivatized, and underivatized plain magnetite nanoparticles did not
induce the same effect on actin filaments and cell proliferation. Whereas
dextran-derivatized and underivatized magnetite nanoparticles induced
a strong inhibition of the BrdU incorporation with disruption of the
F-actin and vinculin filaments, albumin-derivatized nanomagnetite did
not have this effect. Nevertheless, the albumin-derivatized nanomag-
netite did induce vacuole formation in the cell. The dextran shell on the
particles can be broken down, yielding particle chains and aggregates
that may influence cell processes (Berry et al., 2003; Jordan et al., 1996).
This stresses the importance of the nanoparticle’s shell and, conse-
quently, the importance of its stability over time, as the molecular inter-
action between nanoparticles and the environment (Berry et al., 2004a